This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This proposal encompasses the initial structure determination of medically relevant target proteins from the eukaryotic pathogens Trypanosoma bruci (African sleeping sickness). T. cruzi (Chagas disease), Leishmania spp. (leishmaniasis) and Plasmodium spp. (maleria), and follow-up screening of small molecule cocktails to identify chemical fragments that bind at the active site. Initial structure determinations will rely primarily on SeMet MAD/SAD phasing. Screening of cocktail soaks can be done at fixed wavelength, but benifits greatly from the use of robotic automounting and screening.